The primary objective of this research proposal is to determine the mechanisms of action of histocompatibility linked immune response (Ir) genes. For the Ir-1 gene, all mice develop a T cell independent IgM primary response. Responders develop T cell dependent IgG secondary responses whereas nonresponders are suppressed and unreactive to subsequent antigen. These studies have been designed to test the hypothesis that Ir-1 determines T cell recognition sites for carriers; and that carrier activated T cells induce switchover from IgM to IgG in hapten stimulated B cells. 1) Pretreatment of responder mice with hapten inhibits the switchover to IgG. Syngeneic cell transfers will be used to determine whether or not the inhibition is effected by hapten induced depletion of reactive B cells. 2) In nonresponders, an IgM to IgG switchover is induced by GVH across an H-2 barrier. The contribution of T and B cells to this phenomenon will be analyzed by following genetic markers to determine the source of antibody production; by selectively depleting T or B cell populations of host or donor; by testing non H-2 GVH; and by using chemical stimulation of T cells. 3) Nonresponder unreactivity will also be analyzed with syngeneic plasma and cell transfers to isolate the suppression factor for testing against responder cells.